Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine whether glucose metabolic clearance increases and whether catecholamines influence glucose turnover during exercise in total insulin deficiency, 24-h fasted and insulin-deprived pancreatectomized dogs were studied before and during exercise (60 min; 100 m/min; 10% slope) with (n = 8) and without (n = 8) propranolol infusion (PI, 5 micrograms/kg-min). Exercise with or without PI was accompanied by four and fivefold increments in norepinephrine and epinephrine respectively, while glucagon (extrapancreatic) fell slightly. Basal plasma glucose and FFA concentrations and rates of tracer-determined (3[3H]glucose) hepatic glucose production (Ra) and total glucose clearance (including urinary glucose loss) were 459 +/- 24 mg/dl, 1.7 +/- 0.5 mmol/liter, 7.8 +/- 0.9 mg/kg-min and 1.6 +/- 0.1 ml/kg-min, respectively. When corrected for urinary glucose excretion, basal glucose metabolic clearance rate (MCR) was 0.7 +/- 0.1 mg/kg-min and rose twofold (P less than 0.0001) during exercise. Despite lower lactate (3.3 +/- 0.6 vs. 6.6 +/- 1.3 mmol/liter; P less than 0.005) and FFA levels (1.1 +/- 0.2 vs. 2.2 +/- 0.2 mmol/liter; P less than 0.0001) with PI, PI failed to influence MCR during exercise. Ra rose by 3.7 +/- 1.7 mg/kg-min during exercise (P less than 0.02) while with PI the increase was only 1.9 +/- 0.7 mg/kg-min (P less than 0.002). Glucose levels remained unchanged during exercise alone but fell slightly with PI (P less than 0.0001). Therefore, in total insulin deficiency, MCR increases marginally with exercise (13% of normal); the beta adrenergic effects of catecholamines that stimulate both FFA mobilization and muscle glycogenolysis do not regulate muscle glucose uptake. The exercise-induced rise in hepatic glucose production does not require an increase in glucagon levels, but is mediated partially by catecholamines. Present and previous data in normal and alloxan-diabetic dogs, suggest that (a) in total insulin deficiency, control of hepatic glucose production during exercise is shifted from glucagon to catecholamines and that this may involve catecholamine-induced mobilization of peripheral substrates for gluconeogenesis and/or hepatic insensitivity to glucagon, and (b) insulin is not essential for a small exercise-induced increase in muscle glucose uptake, but normal insulin levels are required for the full response. Furthermore, the catecholamines appear to regulate muscle glucose uptake during exercise only when sufficient insulin is available to prevent markedly elevated FFA levels. We speculate that the main role of insulin is not to regulate glucose uptake by the contracting muscle directly, but to restrain lipolysis and thereby also FFA oxidation in the muscle.
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PMID:Regulation of glucose turnover during exercise in pancreatectomized, totally insulin-deficient dogs. Effects of beta-adrenergic blockade. 329 Feb 52

The daily changes in plasma glucose, FFA, insulin and glucagon concentrations in rats under 12 hr-12 hr light-dark conditions, and the role of the suprachiasmatic nucleus (SCN) of the hypothalamus in these changes were examined. In sham-operated rats, the four parameters showed significant daily rhythms. However, after bilateral lesions of the SCN, daily rhythms could not be detected in these parameters under the present experimental conditions. Furthermore, after the SCN lesions the plasma glucose concentration remained at the minimum level of that in sham-operated rats, while the plasma insulin and glucagon concentrations reduced to approximately the mean level and about half the minimum level of sham-operated rats, respectively, and the FFA concentration lowered to somewhat below the minimum level. Gradual increase in the plasma insulin concentration at the end of the light period was observed in intact rats even after starvation for 24 hr. These findings suggest that the SCN is essential for generation of the daily changes in the plasma glucose, FFA, insulin and glucagon concentrations and also that it plays critical roles in regulation of the secretion of pancreatic hormones. The gradual increase in the plasma insulin level observed at the end of the light period is discussed in connection with initiation of spontaneous feeding behaviour.
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PMID:Role of SCN in daily rhythms of plasma glucose, FFA, insulin and glucagon. 332 77

Diazoxide was used to prevent the high insulin secretion after glucagon administration to rabbits. Using of this benzothiadiazine allowed to investigate an effect of glucagon on the blood glucose, free fatty acids and triglycerides without raised insulin. The concentration of serum glucose was increased in all experiments (with or without diazoxide infusion), however both normoinsulinemic and hyperinsulinemic rabbits showed return to the control value in the end of experiments. In the case of FFA the high level of insulin was necessary to return their concentration to the control value. Glucagon alone had no effect on serum TG level.
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PMID:[Use of diazoxide in the studies of the effect of glucagon on the blood serum levels of glucose, free fatty acids and triglycerides in rabbits]. 333 61

Several in vivo studies have indirectly suggested a relationship between blood glutamine and ketonemia. The present study was designed to characterize the role glutamine plays in regulating lipolysis and ketogenesis during fasting in vivo. Twelve dogs had catheters implanted in the hepatic and portal veins (V) and in the femoral artery (A) 17-21 days before study. The animals were fasted for 4 days. After a 120-min rest and 40-min basal periods, 6 dogs received an infusion of L-glutamine at 6 mumol X kg-1 X min-1 and 6 received saline and acted as controls. Hepatic and splanchnic balances (mumol X kg-1 X min-1) were estimated by A-V differences multiplied by blood flow determined by indocyanine green. Fasting was associated with a compensated (no change in pH) mild metabolic acidosis but no change in plasma insulin and glucagon or blood glutamine. L-Glutamine infusion increased blood glutamine by 20% but decreased arterial free fatty acids (FFA, from 1,054 +/- 47 to 850 +/- 43 mumol/l, P less than 0.01), beta-hydroxybutyrate (beta-OHB, from 136 +/- 15 to 66 +/- 8 mumol/l, P less than 0.01), acetoacetate (AcAc, from 168 +/- 26 to 86 +/- 21 mumol/l, P less than 0.01), and glycerol (from 90 +/- 4 to 65 +/- 5 mumol/l, P less than 0.01). It also decreased hepatic uptake of glycerol (from 2.5 +/- 0.5 to 0.8 +/- 0.3 mumol X kg-1 X min-1, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine blocks lipolysis and ketogenesis of fasting. 351 12

The importance of basal cortisol (H) and epinephrine (E) levels on glucoregulation, and the effects of E, given to simulate moderate to severe stress (5 times basal rate of infusion), were examined in seven conscious adrenalectomized dogs. Although plasma glucagon (IRG) increased by 47%, insulin (IRI) decreased by 36%, norepinephrine (NE) increased by 103%, and FFA decreased by 26%, glucose concentration and kinetics remained normal after adrenalectomy. A 4-h infusion of H reestablished basal cortisol levels and returned IRG to its basal preadrenalectomy level with no change in IRI, NE, and FFA levels. Glucose production and metabolic clearance decreased concomitantly by 20%, maintaining euglycemia. A 90-min infusion of basal E caused only a transient increase in IRG. The simultaneous infusion of H with E prevented this increase in IRG and returned IRI to preadrenalectomy levels in the absence of any change in NE or glucose. A subsequent infusion of five times basal E, alone, raised circulating E levels and caused a transient decrease in plasma NE, but no change in IRI. There was a similar hyperglycemic response, as seen previously in normal dogs. The simultaneous infusion of H and E prevented the decrease in NE, but did not change the IRI and FFA responses. There was an 80% greater plasma glucose response than seen during infusion of E alone. In conclusion, what E and H lack after adrenalectomy is compensated for by an increase in IRG and a decrease in IRI, and normal glucose concentrations and kinetics are maintained. It appeared that normoglucagonemia required basal H release, whereas normoinsulinemia required both basal H and E secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucoregulatory role of cortisol and epinephrine interactions studied in adrenalectomized dogs. 351 64

Fasting and postprandial plasma concentrations of glucose, FFA, insulin, glucagon, and GH concentrations were determined in 10 nonobese and 10 obese subjects with normal glucose tolerance. Measurements were made at 0800 h (after a 14-h fast) and at hourly intervals from then until 1600 h. During this time period all individuals ate breakfast at 0800 h (20% of total daily calories) and lunch (40% of total daily calories). Although plasma glucose concentrations were similar throughout the 8-h period in the 2 groups, plasma insulin concentrations were significantly (P less than 0.001) higher in the obese individuals. However, despite the presence of hyperinsulinemia, the obese group also had higher (P less than 0.001) plasma FFA concentration throughout the day. On the other hand, both the absolute and the relative declines in plasma FFA concentration after meals were similar in the 2 groups. Since plasma glucagon and GH concentrations were similar in the 2 groups, altered production of these lipolytic hormones was not responsible for the elevated plasma FFA levels in the obese individuals. These data document the presence in obese individuals of a disassociation in their ability to maintain normal plasma glucose as opposed to plasma FFA homeostasis, and indicate that the increase in plasma FFA concentrations in obesity occurs in the presence of hyperinsulinemia and is not related to abnormalities of either glucagon or GH secretion.
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PMID:Effect of obesity on ambient plasma glucose, free fatty acid, insulin, growth hormone, and glucagon concentrations. 352 20

Plasma glucose, insulin, FFA, glucagon, and GH concentrations were measured over an 8-h period in normal subjects and patients with noninsulin-dependent diabetes mellitus (NIDDM). Meals were consumed at 0800 h (20% of daily calories) and noon (40% of daily calories), and measurements were made hourly from 0800-1600 h. Day-long plasma glucose, insulin, and FFA concentrations were higher than normal (by two-way analysis of variance) in patients with NIDDM, whether obese or nonobese. In addition, day-long plasma glucagon concentrations were also higher than normal (by two-way analysis of variance) in both nonobese and obese patients with NIDDM. Furthermore, direct relationships were found between the total plasma glucagon response from 0800-1600 h and total plasma glucose (r = 0.57; P less than 0.001) and FFA (r = 0.30; P less than 0.06) responses. In contrast, plasma GH levels were not increased in patients with NIDDM. These data demonstrate that ambient plasma concentrations of both glucose and FFA are higher in patients with NIDDM, despite the fact that coexisting plasma insulin levels are equal to or higher than normal. The higher day-long plasma glucagon levels in patients with NIDDM may contribute to their higher plasma glucose and FFA concentrations.
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PMID:Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus. 353 80

Insulin-stimulated glucose disposal was investigated using the euglycemic hyperinsulinemic glucose clamp technique in six women with anorexia nervosa (27.3 +/- 4.9 yr old; weight, 38.8 +/- 6.6 kg) and compared to results obtained in six normal women (22.6 +/- 1.2 yr old; weight, 58 +/- 2.5 kg) and seven obese women (26.8 +/- 7.7 yr old; weight, 92.5 +/- 13.8 kg). The glucose clamp was performed for 2 h using the Biostator and a continuous insulin infusion of 100 mU kg-1 h-1. Plasma levels of insulin were determined at 30-min intervals. Plasma levels of glucagon, FFA, glycerol, 3-hydroxy-butyrate, and alanine were measured basally. Blood glucose levels were similar in normal subjects and anorectic patients; they were slightly but significantly higher in the obese patients. The indices of insulin sensitivity measured were the MCR of glucose and the ratio of glucose infused to insulin infused (G/I). They were very similar in anorectic subjects [MCR, 13.5 +/- 2.4 (+/- SEM) ml kg-1 min-1; G/I, 5.2 +/- 0.9 mg/mU) and normal subjects (MCR, 13.5 +/- 1.7 ml kg-1 min-1; G/I, 5.2 +/- 0.4 mg/mU), but were significantly reduced in obese patients (MCR, 5.1 +/- 0.8 ml kg-1 min-1; G/I, 2.6 +/- 0.3 mg/mU; P less than 0.0025). Differences in plasma insulin among the three groups were not statistically significant. Plasma alanine levels were higher in anorectic than in normal or obese subjects, suggesting defective gluconeogenesis. Thus, insulin-stimulated glucose disposal is normal in patients with anorexia nervosa, a finding that contrasts with the previously reported increase in erythrocyte insulin receptors in this disease.
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PMID:Insulin-stimulated glucose disposal is not increased in anorexia nervosa. 388 Jul 68

In Type I-diabetics metabolic response to exercise is largely determined by the availability of exogenous insulin. The aim of the present study was to assess the metabolic response to moderate exercise of 24 insulin-dependent (Type I-) diabetics treated by multiple subcutaneous injections of short acting insulin. Differences in insulin availability (hypo- [trial A] or hyperinsulinemia [trial B]) resulted from the different periods of time that had elapsed since the previous insulin injection, i.e., after 3 hours (trial A), and 1 hour (trial B). Bicycle ergometer tests at intensities up to 75% VO2max, were carried out with patients and controls. Plasma glucose, FFA, glycerol, alanine, growth hormone and glucagon levels were measured during a period of 85 min. In both trials, physical exertion did not have a significant statistical effect on the glucose concentration in the blood of hypo- and hyperinsulinemics. Surprisingly, despite the different insulin availabilities FFA, glycerol, alanine and glucagon concentrations were not statistically different in either trial and appear similar to those of healthy controls. A normal metabolic response to exercise can thus also be expected in Type I-diabetics, provided adequate insulin is available. When compared to controls, growth hormone concentrations were found to have increased during exercise. These experimental data strongly suggest the great necessity of adequate insulin availability in order to obtain normal metabolic responses to exercise in insulin-dependent diabetics. Despite certain degrees of hypo- or hyperinsulinemia, moderate exercise did not cause any marked metabolic derangements. This type of moderate exercise is therefore recommended for improving metabolic control in such patients.
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PMID:Muscular exercise in type I-diabetics. II. Hormonal and metabolic responses to moderate exercise. 388 16

Thirty-two pigs (1 d old) were used to determine if exogenous glucagon and(or) free fatty acids (FFA oleic acid) would enhance gluconeogenesis and glucose homeostasis during fasting. Pigs were acquired at birth, fitted with an indwelling arterial cannula (via umbilicus) and fasted 24 h to deplete liver glycogen. A jugular cannula was inserted nonsurgically 8 to 10 h before initiation of a primed-continuous infusion consisting of control (excipient), glucagon (Glu), oleic acid (FFA), or both glucagon and oleic acid (Glu-FFA). Plasma Glu averaged 395 pg/ml preinfusion and was similar across treatments. The concentration increased fivefold (P less than .05) by 80 min for Glu and Glu-FFA pigs and remained constant thereafter (160 min: 2,379, 2,258 pg/ml; 240 min: 2,355, 2,274 pg/ml, respectively). Glucagon infusion did not alter plasma glucose after 240 min of infusion (control, 50 vs Glu, 51 mg/dl); however, Glu-FFA effected an increase (60 mg/dl, P less than .10). In contrast, pigs infused with FFA alone had a lower glucose concentration (40 mg/dl, P less than .10). Rate of glucose synthesis was determined using liver slices, acquired immediately postinfusion, with alanine and lactate as substrate (7.5 mM). The rate of synthesis was not altered by Glu or Glu-FFA infusion (2.91, 2.43 mumol glucose X g-1 X h-1 vs 2.91 for control). In contrast, exogenous FFA reduced synthesis to 1.85 mumol glucose X g-1 X h-1 (P less than .05) with lactate as substrate. It appears that Glu is not the primary factor limiting gluconeogenesis in fasting newborn pigs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of exogenous glucagon and free fatty acids on gluconeogenesis in fasting neonatal pigs. 388 18


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